Galactose as a regulatory factor of its own metabolism by rat liver

Rogers, Shirley; Bovee, Brad; Saunders, Steven; Segal, Stanton

doi:10.1016/0026-0495(89)90072-3

Cited by 17 publications

(9 citation statements)

References 26 publications

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“…The large amount of galactose, via lactose, present in rat milk may provide the stimulus for both increasing mRNA and a mechanism for enhancing the enzyme activity. Feeding highgalactose diets to adult rats has been previously shown to increase hepatic GALT sp act (2). However, the relative delay of the maximum of both mRNA and sp act, between d 5 and 7, in contrast to the initiation of galactose intake on d 1, suggests that additional factors may regulate the response of these parameters.…”

Section: Discussionmentioning

confidence: 95%

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Developmental and Tissue-Specific Modulation of Rat Galactose-1-Phosphate Uridyltransferase Steady State Messenger RNA and Specific Activity Levels

et al. 1993

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ABSTRACT. To assess the role of genetic regulation as a state levels of GALT sp act (7). In this report, we have assessed modulating factor in the variability of rat tissue galactose-GALT sp act and steady state mRNA during postnatal rat liver I-phosphate uridyltransferase (GALT) sp act, we have development and in various tissues of the adult rat. Our findings determined steady state GALT mRNA and sp act in rat that there is a correlation between the two parameters in these liver during postnatal development. Steady state GALT investigations indicates that genetic regulation plays an impormRNA levels increase from birth to d 5 and subsequently tant role in modulating GALT activity. Our findings form the decrease toward adult levels. GALT sp act mirrors the basis of this report. mRNA pattern. A survey of steady state mRNA and GALT sp act of several adult rat tissues revealed marked tissue differences with a good correlation of the two parameters. MATERIALS A N D M E T H O D SLiver had the highest GALT mRNA and sp act; kidney, ..lnimul.s. Timed pregnant Sprague-Dawley rats from Charles ovary, a_nd heart had similar but lower mRNA and sp act; River Breeding Farms (Wilmington. MA) were housed three per skeletal muscle and testes had the least GALT mRNA and cage with free access to food and water in a room with a 10: 14 enzyme sp act. These findings suggest that genetic regu-h 1ight:dark cycle. All experiments were performed using the lirtion is important in the variable expression of GALT Children' Chomczynski and Sacchi (8). One hundred mg of tissue were homogenized using a Dounce homogenizer in 1 The metabolism of galactose, a major carbohydrate constituent mL of 4 M guanidinium thiocyanate. 25 mM sodium citrate. of almost all animal milk, is controlled by the three enzymes of pH 7, 0.5% SDS, and O.' 2-mercapt0ethan01. The tissue was the Leloir pathway, galactokinase, GALT, and UDP galactose-transferred to a ~ol~pr0pYlene tube and sequentially extracted 4-epimerase ( 1). ~h~~ GALT is a key enzyme in the pathway is with acidified phenol and chloroform-isoamyl alcohol (49: 1). highlighted by human galactosemia due to deficient GALT ac-The RNA was precipitated with isopropanol and resuspended in tivity. Interest in this recessively inherited disorder has fostered 1 mL of dieth~l~~rocarbonate-treated water. The RNA concenefforts to delineate the mechanism responsible for regulation of tration was determined by at 260 nm UV.GALT activity. We have previously described increases in liver Separate Northern blots of RNA obtained from newborn rat GALT sp act in rats fed a highegalactose diet (2). in pregnant liver and adult rat tissues were generated by electrophoresis of female rat liver, possibly related to progesterone (3. 4), and in l o pg RNA a I% agarOse-fomaldehYde gel the postnatal development of rat liver (5). We have also described by a Zetabind membrane (CUNO. variation of GALT sp act in different rat tissues (5) and modu-Meriden, CT). The RNA was fixed to the membrane using a lation by uridine nucleotides (6). ...

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Section: Discussionmentioning

confidence: 95%

“…We have previously described increases in liver Separate Northern blots of RNA obtained from newborn rat GALT sp act in rats fed a highegalactose diet (2). in pregnant liver and adult rat tissues were generated by electrophoresis of female rat liver, possibly related to progesterone (3.…”

Section: Materials a N D M E T H O D Smentioning

confidence: 99%

Developmental and Tissue-Specific Modulation of Rat Galactose-1-Phosphate Uridyltransferase Steady State Messenger RNA and Specific Activity Levels

et al. 1993

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“…The complete carbohydrate chains which contain galactose and GalNAc to which sulfate and sialic acid are bound are necessary for biological function [24,25], The present findings provide a possible biochemical basis for the ovarian failure observed in most female patients with galactosemia [26][27][28] and the critical role of GALT for normal ovarian development and function. This may concern GALT in the ovaries where GALT is 5 times more expressed than in testis [4] but also in tissues associated with ovary function, i.e. the anterior pituitary gland.…”

Section: Discussionmentioning

confidence: 99%

“…GALT-specific enzy matic activity and activation of galactose metabolism. This has been demonstrated in the liver during postnatal development [2,3] and in response to a high galactose diet [4], GALT mRNA expression has also been shown to be correlated to GALT enzymatic activity investigated in different regions of rat brain [5] and various other tissues, including testis and ovary from adult rats [3], In the present study we concentrated on GALT mRNA and protein expression in rat anterior pituitary at differ ent stages of the estrous cycle. Levels of synthesis of pitu itary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) change during estrous cycle, with a translational peak during diestrus [6][7][8][9][10][11] and a transcriptional peak in proestrus and early estrus [7][8][9], The peak of LH and of FSH release occurs during late proestrus and estrus [12,13].…”

Section: Introductionmentioning

confidence: 99%

Expression of Galactose-1-Phosphate Uridyltransferase in the Anterior Pituitary of Rat during the Estrous Cycle

Daude¹,

Lestage²,

Reichardt³

et al. 1996

Neuroendocrinology

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Biological activity of the follicle-stimulating hormone (FSH) is dependent on its pattern of glycosylation and is altered during galactosemia, a genetic disease characterized by deficient activity of galactose-1-phosphate uridyltransferase (GALT). To assess the role of this enzyme in the synthesis of FSH, the expression of GALT at the mRNA and protein levels was measured in the whole anterior pituitary during the estrous cycle of rat. GALT was maximally expressed during the proestrous and estrous phases of the estrous cycle. The expression pattern of GALT was associated with gonadotropin-expressing cells. This close association is in accordance with the postulated role of GALT in modulating biological activity of FSH.

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“…Fasting also significantly decreased lactate release in the control incubations performed without added substrate at these same ages. Galactose supplementation of the suckling diet has previously been shown to enhance the activity of galactose-catabolizing enzymes in intestine (1 5 ) as well as in liver (16). To determine whether the decreased lactate formation of fasted animals was the result of a decreased glycolytic rate or the altered activity of Leloir enzymes plus phosphoglucomutase (EC 5.4.2.2) or fructokinase (EC 2.7.1.4) plus aldolase-B (fructose-1-phosphate aldolase.…”

Section: Resultsmentioning

confidence: 99%

Lactate Genesis by Rat Liver and Muscle during Development

Dombrowski

Swiatek

1991

Pediatr Res

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ABSTRACT. Lactate has been shown to be an important fuel for brain metabolism during early postnatal development (1). In an attempt to identify the source(s) of lactate in the postnatal rat, we have studied the in vitro catabolism of glucose, galactose, fructose, alanine, glycerol, and octanoate in liver and muscle minces prepared from suckling rat pups. Whereas galactose, fructose, and octanoate were found to be lactagenic (lactate generating) in liver, glucose was the sole lactate precursor in muscle. Galactose was most effective a s a hepatic lactate source a t 3 d of age. Thereafter, the production of lactate from galactose decreased to reach control levels by 1 5 d of age. In contrast, fructose or octanoate were lactagenic throughout development. Lactate formation from galactose was completely halted by iodoacetate, inhibited by high galactose concentrations, and suppressed by fasting. The absence of oxygen increased lactate production from either fructose or octanoate, but it did not affect lactagenesis from galactose. Muscle minces produced lactate from glucose in an agedependent manner similar to the development pattern of lactate formation from galactose by liver. Because lactosederived galactose is readily available during suckling, it is suggested that galactose-based hepatic lactagenesis serves a unique role in maintaining the supply of lactate during early postnatal development. This hepatic capability may augment glucose-based muscle lactate synthesis at a time when lactate is a major brain fuel. (Pediatr Res 30: 331-336, 1991) Abbreviations UDP, uridine diphosphate Lactate is the major fuel for brain cortex in rat pups during the first postpartum week (I). The utilization of lactate accounts for more than 70% of cerebral oxidative metabolism in the 6-dold, normally ventilated rat pup, followed by the consumption of 3-hydroxybutyrate and glucose in approximately equal amounts. The extensive reliance of the young cerebral cortex upon lactate as a fuel prompted this investigation to evaluate the lactagenic' potential of several common metabolites when supplied to liver or muscle during the postnatal period.Milk, the sole food source available to suckling pups, consists principally of casein, fats, and sugars. Although fats comprise 70-80% of the caloric content of milk, it is most probable that a sugar provides the carbon for lactate synthesis. Lactose, a disaccharride of glucose and galactose, is the principal milk sugar.Although glucose-derived muscle lactagenesis is known, there is n o information available concerning the relative output of lactate from skeletal muscle as a function of age during the suckling period. In investigations of galactose metabolism during development, the primary emphasis has been the genesis of glucose in fasted animals (2-4). Even though it has been known for many years that the i.v. administration of galactose to infants results in the physiologic elevat~on of blood lactate levels (5), no attempt has been made to delineate the mechanism of this phenomenon or explain i...

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Galactose as a regulatory factor of its own metabolism by rat liver

Cited by 17 publications

References 26 publications

Developmental and Tissue-Specific Modulation of Rat Galactose-1-Phosphate Uridyltransferase Steady State Messenger RNA and Specific Activity Levels

Developmental and Tissue-Specific Modulation of Rat Galactose-1-Phosphate Uridyltransferase Steady State Messenger RNA and Specific Activity Levels

Expression of Galactose-1-Phosphate Uridyltransferase in the Anterior Pituitary of Rat during the Estrous Cycle

Lactate Genesis by Rat Liver and Muscle during Development

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